Evidence derived from clinical observations indicates that small numbers of tumor cells can exist in a dormant state in clinically normal persons or can persist in patients receiving anti-tumor therapy who have attained clinical tumor remissions. Little is known of the host-tumor cell interactions that result in the establishment of this dormant tumor state. We have observed delayed tumor emergence in mice immunized against a syngeneic chemically-induced lymphoma. The mice were immunized with mitomycin C-treated lymphoma cells and then challenged 14 days later with a dose of live tumor that killed 100 percent of unimmunized mice in less than 28 days. In contrast, over 95 percent of immunized mice resisted the immediate outgrowth of the tumor and remained clinically normal for many months. However, during this 18 month period about 40 percent of such mice developed large ascitic tumors. Control groups of immunized but unchallenged mice and untreated mice observed for similar periods remained completely free of such tumors. We propose to use this model system to (1) identify the host immune and non-immune components that act on tumor cells to establish and maintain the tumor-dormant state and (2) characterize the events that lead to breakdown of the tumor-dormant state and outgrowth of tumor. An understanding of the interactions involved in tumor dormancy should greatly facilitate the development of methods for prolonging the tumor-dormant period and, ultimately, the complete elimination of residual tumor cells.